Journal of Alzheimer's Disease - Volume 60, issue s1

Authors: Valero, Jorge | Bernardino, Liliana | Cardoso, Filipa Lourenço | Silva, Ana Paula | Fontes-Ribeiro, Carlos | Ambrósio, António Francisco | Malva, João Oliveira

Article Type: Review Article

Abstract: The cognitive reserve is associated with the capacity of the brain to maintain cognitive performance in spite of being challenged by stressful degenerative insults related to aging. Hippocampal neurogenesis is a life-long process of continuous addition of functional new neurons in the memory processing circuits. Accordingly, adult hippocampal neurogenesis is increasingly seen as a key determinant of cognitive reserve robustness. On the other side, neuroinflammation, by releasing a plethora of proinflammatory cytokines and other inflammatory molecules, is increasingly shown to be one of the key determinant pathophysiological factors that negatively impact on neurogenesis and on the cognitive reserve, playing a …detrimental role in hippocampal neurogenic niche dynamics and in the progression of neurodegenerative diseases, such as Alzheimer’s disease. In the present manuscript, we highlight the functional interplay between neuroinflammation, dynamics of the neurogenic niche, and spatial memory performance in healthy and age-related pathological processes, including progression of Alzheimer’s disease. Show more

Keywords: Aging, Alzheimer’s disease, memory, neural stem cells, neurogenesis, neuroinflammation

DOI: 10.3233/JAD-170239

Citation: Journal of Alzheimer's Disease, vol. 60, no. s1, pp. S161-S168, 2017

Authors: Nookala, Anantha Ram | Mitra, Joy | Chaudhari, Nitish S. | Hegde, Muralidhar L. | Kumar, Anil

Article Type: Review Article

Abstract: With increasing survival of patients infected with human immunodeficiency virus type 1 (HIV-1), the manifestation of heterogeneous neurological complications is also increasing alarmingly in these patients. Currently, more than 30% of about 40 million HIV-1 infected people worldwide develop central nervous system (CNS)-associated dysfunction, including dementia, sensory, and motor neuropathy. Furthermore, the highly effective antiretroviral therapy has been shown to increase the prevalence of mild cognitive functions while reducing other HIV-1-associated neurological complications. On the contrary, the presence of neurological disorder frequently affects the outcome of conventional HIV-1 therapy. Although, both the children and adults suffer from the post-HIV treatment-associated …cognitive impairment, adults, especially depending on the age of disease onset, are more prone to CNS dysfunction. Thus, addressing neurological complications in an HIV-1-infected patient is a delicate balance of several factors and requires characterization of the molecular signature of associated CNS disorders involving intricate cross-talk with HIV-1-derived neurotoxins and other cellular factors. In this review, we summarize some of the current data supporting both the direct and indirect mechanisms, including neuro-inflammation and genome instability in association with aging, leading to CNS dysfunction after HIV-1 infection, and discuss the potential strategies addressing the treatment or prevention of HIV-1-mediated neurotoxicity. Show more

Keywords: AIDS, cognitive dysfunction, dementia, genome instability, human immunodeficiency virus type 1, neurodegeneration

DOI: 10.3233/JAD-170473

Citation: Journal of Alzheimer's Disease, vol. 60, no. s1, pp. S169-S193, 2017

Authors: Periyasamy, Sabapathy | Sathya, Mohan | Karthick, Chennakesavan | Kandasamy, Mahesh | Shanmugaapriya, Sellathamby | Tamilselvan, Jeyavelu | Jayachandran, Kesavan Swaminathan | Anusuyadevi, Muthuswamy

Article Type: Research Article

Abstract:  Epidemiological studies state that dementia has multiple etiologies including genetic mutation, genetic variation, and environmental factors. Accumulating evidence suggests that dysregulation of cholesterol homeostasis is the major etiological factor in initiating neurodegeneration. Apolipoprotein E (APOE) polymorphic alleles and associated polymorphism of lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) that are important components in regulating cholesterol metabolism are implicated in neurodegenerative diseases. Therefore, the current study focused on identifying the association between several common polymorphism (viz., APOE, CETP, and LPL) to that of change in serum lipid levels and memory symptoms. Volunteer subjects aged 50 and above from rural …and tribal areas of the Dharmapuri district, Tamilnadu, India were chosen for the current study and polymorphism was analyzed using PCR-RFLP. Fasting lipid profile and memory function using simplified version of Global Clinical Dementia rating were assessed. Significant difference in the major lipid profile parameters were observed (TC, TGL, LDL, VLDL) among rural and tribal populations that were associated with significant genotypic variation of APOE, CETP, and LPL. Regression analysis revealed significant risk for memory loss that are dependent on age and genetic variants like CETP. These data predict positive correlation between cholesterol-associated genes and their relationship to altered lipid profile and memory symptoms, which possibly link gene-polymorphism and susceptibility ratio for aging and dementia. Show more

Keywords: Alzheimer’s disease, apolipoprotein E, cholesteryl ester transfer protein, lipid profile, lipoprotein lipase, memory, polymorphism

DOI: 10.3233/JAD-170272

Citation: Journal of Alzheimer's Disease, vol. 60, no. s1, pp. S195-S207, 2017

Authors: Prema, Asokan | Justin Thenmozhi, Arokiasamy | Manivasagam, Thamilarasan | Mohamed Essa, Musthafa | Guillemin, Gilles J.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a common neurodegenerative disorder that mainly affects the aged population and is characterized by the progressive loss of the hippocampal and cortical neurons, which results in memory and cognitive impairments. Trigonella foenum-graecum (fenugreek) has been reported to have hypoglycemic, hypocholesterolemic, hyperinsulinemic and anti-diabetic properties. Traditionally, it was used as a galactagogue and to treat anorexia, fever gastritis, gastric ulcers, and various nervous disorders. However, the neuroprotective effect of fenugreek seed powder against aluminum chloride (AlCl3 ) induced AD rats has not been analyzed. The result of the present study indicated that the chronic administration of …AlCl3 induced significant learning and memory impairments, oxidative stress, and alterations in the protein immunocontent patterns of IDE and CDK5 (enzymes involved in the metabolism of tau and amyloid proteins), pTau, GFAP and Iba-1, IL-1β, IL-6, TNF-α, iNOS, NF-κ B, COX-2, CDK5, BDNF, and STAT3. Our behavioral, biochemical, and molecular studies revealed that the co-administration of fenugreek seed powder significantly attenuated the AlCl3 induced memory deficits, amyloid and tau pathology, oxidative stress, and inflammation in AD rats could be due to the synergistic action of its active components. Show more

Keywords: Alzheimer’s disease, fenugreek seeds, inflammation, neuroprotection, oxidative stress tau pathology

DOI: 10.3233/JAD-161103

Citation: Journal of Alzheimer's Disease, vol. 60, no. s1, pp. S209-S220, 2017

Authors: Zaky, Amira | Bassiouny, Ahmad | Farghaly, Mahitab | El-Sabaa, Bassma M.

Article Type: Research Article

Abstract: Background: Experimental studies have demonstrated that aluminum is an environmental toxin that induces neuroinflammation and the development of Alzheimer’s disease. Objective: In this report, we investigated the beneficial effect of a combination of resveratrol and curcumin to reduce aluminum-induced neuroinflammation. Method: We employed both an in vivo model of aluminum-induced neuroinflammation and an in vitro aluminum stimulated cultured PC-12 cells. Neuroinflammation in rats was assessed by measuring the expression of β-secretase, amyloid-β protein precursor, and γ -subunits (PS-1 and PS-2), along with the inflammatory COX-2, Il-1β, Il-1α, and TNF-α. Furthermore, we measured the expression profiles of neuro-protective …Apurinic/apyrimidinic endonuclease 1 (APE1) protein and let-7c microRNA. In parallel, PC-12 cells were treated with 0.5 mM aluminum to induce a neuroinflammation-like state. In addition, curcumin effect, as a selective COX-2 expression inhibitor, was detected in a time course manner. Results: An overall significant attenuation of the inflammatory markers, as well as a decrease in the amyloidogenic mediators, was observed in resveratrol-curcumin treated rats. The therapeutic effect was also confirmed by transmission electron microscopic analysis of the brain cortexes. APE1 was significantly induced by resveratrol-curcumin combination. Both in vivo and in vitro studies indicated that Let-7c expression is significantly reduced after aluminum stimulation, an effect that was partially suppressed by co-addition of either resveratrol or curcumin and totally restored to the normal level by their combination. Conclusions: The present study clearly indicates the synergistic and therapeutic effect of a  resveratrol-curcumin combination. We also show that both compounds exert beneficial effect either cooperatively or through differential molecular mechanisms in counteracting aluminum-induced neuroinflammation. Show more

Keywords: Aluminum, apurinic/apyrimidinic endonuclease 1, curcumin, cyclooxygenase-2, microRNA Let-7c, resveratrol

DOI: 10.3233/JAD-161115

Citation: Journal of Alzheimer's Disease, vol. 60, no. s1, pp. S221-S235, 2017